Barium dilaurate

Endpoint summary

Key value for chemical safety assessment

Genetic toxicity in vitro

Description of key information

No genetic toxicity study with barium dilaurate is available, thus the genetic toxicity will be addressed with existing data on the assessment entities barium and lauric acid. Barium dilaurate is not expected to be genotoxic, since the two assessment entities barium and laurate have not shown gene mutation potential in bacteria and mammalian cells as well as in vitro clastogenicity.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (negative)

Genetic toxicity in vivo

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Barium

None of the in vitro genotoxicity studies rated as reliable showed any effect in bacterial reverse mutation assays, in mammalian cell gene mutation tests (TK assay) or in mammalian cell chromosome aberration tests, thus the classification criteria according to regulation (EC) 1272/2008 as germ cell mutagen are not met.

 

in vitro clastogenicity

Based on the outcome of guideline-compliant studies barium dichloride does not induce chromosome aberrations in mammalian cells, when tested up to toxic and/or precipitating concentrations in two independent experiments in the absence and presence of a rat liver metabolic activation system (S9 mix).

Overall it can be concluded that barium dichloride does not induce chromosome aberrations in vitro in somatic mammalian cells. Therefore the conduct of in vivo clastogenicity experiments is not required.

 

 

in vitro gene mutation

Anonymous (1994)

The authors state that barium dichloride induces gene mutations in cultured mouse lymphoma cells (L5178Y) in the presence of S9 in a statistical significant manner. However, the mutation frequency increased from 32 per 106

cells in the control culture to a maximum of 59 per 106 cells at 1000µg/mL (with a RTG of 10%). Being a statistical significant increase in mutation frequency, the biological significance however is considered questionable, since the highest MF is still well below the value recommended by the IWGT (Moore et al., 2003; Moore et al., 2006; Moore et al., 2007) of 154 per 106 cells. Furthermore, a comparison with historical data for the performing laboratory is not possible, since the data was not given in the study report.

Due to the questionable biological relevance, the statistical significant increase in mutation frequency in both barium dichloride cultures with metabolic activation is not considered as clear positive response. Therefore, it was decided to repeat the whole experiment under clearly defined conditions, which a highly pure test item under guideline and GLP compliant conditions.

 

Lloyd (2010)

It is concluded that barium dichloride did not induce gene mutations in the TK locus of L5178Y mouse lymphoma cells when tested up to toxic and/or precipitating concentrations in two independent experiments in the absence and presence of a rat liver metabolic activation system (S9 mix).

Overall it can be concluded that barium dichloride does not induce gene mutations in vitro in bacteria and somatic mammalian cells. Therefore, the conduct of in vivo gene mutation experiments is not required.

 

 

References

Moore M et al. (2003)

Mouse lymphoma thimidine kinase gene mutation assay: International workshop on Genotoxicity tests workgroup report – Plymouth, UK 2002. Mutation Research (2003), 540, 127-140.

 

Moore M M, Honma M, Clements J, Bolcsfoldi G, Burlinson B et al. (2006)

Mouse lymphoma thymidine kinase gene mutation assay: follow up meeting of the International Workshop on Genotoxicity Testing – Aberdeen, Scotland, 2003 – Assay acceptance criteria, positive controls, and date evaluation. Environmental and Molecular Mutagenesis 2006, 47, 1-5.

 

Moore M M, Honma M, Clements J, Bolcsfoldi G, Burlinson B et al. (2007)

Mouse lymphoma thymidine kinase gene mutation assay: meeting of the International Workshop on Genotoxicity Testing, San Francisco, 2005, recommendations for 24-h treatment. Mutation Research 2007, 627, 36-40.

Laurate

Based on in vitro data the HERA document on fatty acid salts (2002) reported that “fatty acids are negative in in vitro bacterial systems used in the Ames test (BIBRA, 1988; BIBRA, 1996). In addition, saturated fatty acids up to and including C12, and the unsaturated acid C18:1, have shown inhibition of the mutagenic activity of N-nitrosodialkylamines on Eschericha coli (Negishi et al. 1984). Also, fatty acids from C12 up to C19 have shown anticlastogenic effects in the chromosome aberration test (Renner, 1986)” (HERA, 2002).

“In the study by Zeiger et al. (1988), lauric acid (purity 99%) was assessed for its mutagenicity in the reverse mutation assay using S. Typhimurium strains TA1535, TA1537, TA97, TA98 and TA100 up to a maximum concentration of 666 µg/plate in DMSO, both in the absence and presence of rat and Chinese hamster S9 metabolic activation at 10% or 30%, and no mutagenicity was observed” (EFSA ANS Panel, 2017).

 

“Lauric acid (C12) has shown negative results in the Ames test using Salmonella typhimurium with and without metabolic activation at concentrations up to 2500 µg/plate. (IUCLID, 2000a)” (HERA, 2002).

Additionally, no genotoxicity was observed in animal experiments with fatty acids with similar chain lengths, such as decanoic (C10) acid or tetradecanoic (C14) acid.

“Capric acid (C10) produced negative results in the Ames test using Salmonella typhimurium strains TA97, TA98, TA100, TA1535 and TA1537 at concentrations ranging from 0-666 µg/plate, with and without metabolic activation (IUCLID, 2000c). It also produced negative results in the Escherichia coli reverse mutation assay without activation (IUCLID, 2000c)” (HERA, 2002).

 

Overall, it was considered by the EFSA ANS Panel as well as HERA that the available data did not raise a concern for genotoxicity of fatty acids and their salts.

 

Barium dilaurate

Barium dilaurate is not expected to be genotoxic, since the two moieties barium and laurate have not shown gene mutation potential in bacteria and mammalian cells as well as in vitro clastogenicity. Further testing is not required. Thus, barium dilaurate is not to be classified according to regulation (EC) 1272/2008 as genetic toxicant. For further information on the toxicity of the individual constituents, please refer to the relevant sections in the IUCLID and CSR.

Justification for classification or non-classification

Barium dilaurate is not to be classified according to regulation (EC) 1272/2008 as genetic toxicant, since all in vitro and in vivo studies with the respective assessment entities did not show any gene mutation potential.